The overall objective of this program is to investigate relationships between blood coagulation and the pathogenesis of intravascular clotting and of localized thrombosis. The program is divided into biochemical, physiological and clinical projects. Purified human clotting proteins--factor VII, factor IX, factor X, and Protein C--are utilized in the biochemical projects in studies of the mechanisms of initiation and regulation of the blood coagulation reactions. The biochemical projects include: (1) A study of whether activation of human factor VII is an absolute requirement for its enzymatic activity, (2) A study of mechanisms of activation of factor VII during clotting, (3) A study of activation of factor VIII by factor Xa, phospholipid and Ca2 ion, (4) A study of the activation of human Protein C, (5) A study of the possible effects of activated Protein C in whole plasma clotting systems. The physiological projects are focused upon studies of cell surface tissue factor activity and cell surface tissue factor antigen in stimulated and unstimulated human monocyte cell suspensions. Binding of radiolabelled purified clotting factors to monocyte cell surfaces is to be related to the surface tissue factor activity of the cells. Specific physiologic projects include: (1) A study of binding of factor VII to monocyte cell surface tissue factor, (2) A study of the interaction of monocyte cell surface tissue factor with nature and activated factors IX and X, (3) A study of binding of Fab fragment specific for human tissue factor apoprotein to monocytes. The clinical projects include: (1) measurement of Protein C in clinical disorders, (2) studies of circulating tissue factor in clinical disorders, and (3) A study of the effect of specific antibodies upon the coagulant properties of factor IX concentrates.